Towards development of novel immunization strategies against leishmaniasis using PLGA nanoparticles loaded with kinetoplastid membrane protein-11

Background: Vaccine development has been a priority in the fight against leishmaniases, which are vector-borne diseases caused by Leishmania protozoa. Among the different immunization strategies employed to date is inoculation of plasmid DNA coding for parasite antigens, which has a demonstrated ability to induce humoral and cellular immune responses. In this sense, inoculation of plasmid DNA encoding Leishmania kinetoplasmid membrane protein-11 (KMP-11) was able to confer protection against visceral leishmaniasis. However, recently the use of antigen delivery systems such as poly(lactic-co-glycolic acid) (PLGA) nanoparticles has also proven effective for eliciting protective immune responses. Methods: In the present work, we tested two immunization strategies with the goal of obtaining protection, in terms of lesion development and parasite load, against cutaneous leishmaniasis caused by L. braziliensis. One strategy involved immunization with plasmid DNA encoding L. infantum chagasi KMP-11. Alternatively, mice were primed with PLGA nanoparticles loaded with the recombinant plasmid DNA and boosted using PLGA nanoparticles loaded with recombinant KMP-11. Results: Both immunization strategies elicited detectable cellular immune responses with the presence of both proinflammatory and anti-inflammatory cytokines; mice receiving the recombinant PLGA nanoparticle formulations also demonstrated anti-KMP-11 IgG1 and IgG2a. Mice were then challenged with L. braziliensis, in the presence of sand fly saliva. Lesion development was not inhibited following either immunization strategy. However, immunization with PLGA nanoparticles resulted in a more prominent reduction in parasite load at the infection site when compared with immunization using plasmid DNA alone. This effect was associated with a local increase in interferon-gamma and in tumor necrosis factor-alpha. Both immunization strategies also resulted in a lower parasite load in the draining lymph nodes, albeit not significantly. Conclusion: Our results encourage the pursuit of immunization strategies employing nanobased delivery systems for vaccine development against cutaneous leishmaniasis caused by L. braziliensis infection. © 2012 Santos et al, publisher and licensee Dove Medical Press Ltd.Government of Navarra; CAN Foundation and CYTEDPeer Reviewe

Estudos sobre a paz e cultura da paz

Segundo o autor, a cultura da paz implica uma mudança quer na forma como a “alta cultura” lida com a realidade quer no tipo de abordagem que o senso comum faz às relações sociais, sendo que a ruptura com a ideologia conservadora, ou seja, com o senso comum realista só é possível graças a estas alterações. O autor realça tanto a importância que os estudos sobre a paz têm para o surgimento de um conceito amplo de paz, desenvolvido por Johan Galtung, como o facto destes estarem estrategicamente orientados para a transformação do sistema internacional. Sequentemente, conclui que a paz é uma categoria moral e cultural que só pode ser alcançada através do comportamento quotidian

Characterization and modulation of microglial phenotypes in an animal model of severe sepsis

We aim to characterize the kinetics of early and late microglial phenotypes after systemic inflammation in an animal model of severe sepsis and the effects of minocycline on these phenotypes. Rats were subjected to CLP, and some animals were treated with minocycline (10 ug/kg) by i.c.v. administration. Animals were killed 24 hours, 5, 10 and 30 days after sepsis induction, and serum and hippocampus were collected for subsequent analyses. Real-time PCR was performed for M1 and M2 markers. TNF-α, IL-1β, IL-6, IL-10, CCL-22 and nitrite/nitrate levels were measured. Immunofluorescence for IBA-1, CD11b and arginase was also performed. We demonstrated that early after sepsis, there was a preponderant up-regulation of M1 markers, and this was not switched to M2 phenotype markers later on. We found that up-regulation of both M1 and M2 markers co-existed up to 30 days after sepsis induction. In addition, minocycline induced a down-regulation, predominantly, of M1 markers. Our results suggest early activation of M1 microglia that is followed by an overlap of both M1 and M2 phenotypes and that the beneficial effects of minocycline on sepsis-associated brain dysfunction may be related to its effects predominantly on the M1 phenotype

Metabolite Profiles of Sugarcane Culm Reveal the Relationship Among Metabolism and Axillary Bud Outgrowth in Genetically Related Sugarcane Commercial Cultivars

Metabolic composition is known to exert influence on several important agronomic traits, and metabolomics, which represents the chemical composition in a cell, has long been recognized as a powerful tool for bridging phenotype–genotype interactions. In this work, sixteen truly representative sugarcane Brazilian varieties were selected to explore the metabolic networks in buds and culms, the tissues involved in the vegetative propagation of this species. Due to the fact that bud sprouting is a key trait determining crop establishment in the field, the sprouting potential among the genotypes was evaluated. The use of partial least square discriminant analysis indicated only mild differences on bud outgrowth potential under controlled environmental conditions. However, primary metabolite profiling provided information on the variability of metabolic features even under a narrow genetic background, typical for modern sugarcane cultivars. Metabolite–metabolite correlations within and between tissues revealed more complex patterns for culms in relation to buds, and enabled the recognition of key metabolites (e.g., sucrose, putrescine, glutamate, serine, and myo-inositol) affecting sprouting ability. Finally, those results were associated with the genetic background of each cultivar, showing that metabolites can be potentially used as indicators for the genetic background

Conhecimento materno sobre aleitamento: um estudo piloto realizado em Salvador, Bahia visando à elaboração de uma cartilha educativa

Although breast milk is the best food for the infants, maternal misinformation about the importance of breastfeeding is remarkable. We aimed to evaluate the knowledge of mothers and pregnant women about breastfeeding and to elaborate an educative booklet addressing the most important doubts identified in this population. A qualitative study was idealized and developed by Medicine graduating students of UFBA, attending at Preventive and Social Paediatrics' discipline. We studied a convenience sample, not probabilistic, composed by 24 mothers and pregnant women, using a semi-structured questionnaire elaborated by the authors to personal interview. The studied group presented doubts and misinformation about the subject, chiefly those related to breast preparing and feeding position (70.8%), besides the correct moment to introduce new foods (67.0%). The use of tea, water and juices before the sixth month is very frequent (50.0%), while 25.0% of the participants were afraid to have insufficient breast milk. Based on these data, an educative booklet was elaborated. We verified that the level of mothers' information about breastfeeding remains rather low in spite of the campaigns and the progress on scientific knowledge about the topic. The construction of an informative booklet should contribute to the enlightenment of the most important doubts about breastfeeding.Embora o leite materno seja o melhor alimento para a criança, é notável o desconhecimento das mães sobre a importância da amamentação. Foram objetivos do estudo: (1) avaliar o conhecimento de mães e gestantes acerca da amamentação e (2) elaborar uma cartilha que contemplasse as principais dúvidas identificadas. Um estudo qualitativo foi idealizado e desenvolvido por alunos de graduação em Medicina da UFBA, no curso da disciplina de Pediatria Preventiva e Social. Estudou-se uma amostra de conveniência, não probabilística, composta por 24 mães e gestantes. Utilizou-se questionário semi-estruturado, elaborado pelos autores, para entrevista pessoal. O grupo estudado apresentou diversas dúvidas e desconhecimentos acerca do tema, destacando-se aqueles relacionados ao preparo da mama e posição de amamentar (70,8%), além do momento correto para introdução de novos alimentos (67,0%). O uso de chá, água e sucos antes do sexto mês é ainda muito freqüente (50,0%) entre os lactentes, e 25,0% das mulheres temiam não ter leite suficiente. A partir desses dados, elaborou-se a cartilha informativa. Verificou-se que o nível de informação das mães sobre a amamentação é insuficiente, apesar das campanhas veiculadas pela mídia e do avanço no conhecimento científico sobre o tema. A construção de uma cartilha informativa deve contribuir no esclarecimento das principais dúvidas acerca de amamentação

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19

Immunity to Lutzomyia intermedia Saliva Modulates the Inflammatory Environment Induced by Leishmania braziliensis

Transmission of Leishmania parasites occurs during blood feeding, when infected female sand flies inject humans with parasites and saliva. Chemokines and cytokines are secreted proteins that regulate the initial immune responses and have the potential of attracting and activating cells. Herein, we studied the expression of such molecules and the cellular recruitment induced by salivary proteins of the Lutzomyia intermedia sand fly. Of note, Lutzomyia intermedia is the main vector of Leishmania braziliensis, a parasite species that causes cutaneous leishmaniasis, a disease associated with the development of destructive skin lesions that can be fatal if left untreated. We observed that L. intermedia salivary proteins induce a potent cellular recruitment and modify the expression profile of chemokines and cytokines in mice. More importantly, in mice previously immunized with L. intermedia saliva, the alteration in the initial inflammatory response was even more pronounced, in terms of the number of cells recruited and in terms of gene expression pattern. These findings indicate that an existing immunity to L. intermedia sand fly induces an important modulation in the initial immune response that may, in turn, promote parasite multiplication, leading to the development of cutaneous leishmaniasis